The movement of fluids through channels on a micro scale has important implications in a number of technologies. For example, in the field of molecular biology, polymerise chain reactions (PCR) have been performed in a chip containing microfabricated flow channels (U.S. Pat. Nos. 5,498,392; 5,587,128; 5,726,026). In the electronics field, thermal ink jet printers use printheads with microchannels through which ink must flow in a well controlled manner (U.S. Pat. No. 5,119,116). Proper control of fluids through microchannels has been a challenge, with microdimensions imparting difficulties not encountered at larger scales.
The publications and other materials used herein to illuminate the background of the invention or provide additional details respecting the practice, are incorporated by reference, and for convenience are respectively grouped in the appended List of References.
Surface effects describe the character of a surface on a micro scale. Materials often have unbound electrons, exposed polar molecules, or other molecular level features that generate a surface charge or reactivity characteristic. Due to scaling these surface effects or surface forces are substantially more pronounced in micro structures than they are in traditionally sized devices. This is particularly true in micro scale fluid handling systems where the dynamics of fluid movement are governed by external pressures and by attractions between liquids and the materials they are flowing through. This fact can be utilized to fabricate unique structures that function due to these surface forces.
This invention deals with the passive control of fluids within a microfluidic circuit. The passive control is generated by using the natural forces that exist on a micro scale, specifically capillarity, which is caused by the attraction or repulsion of a fluid toward certain materials. The purpose is to stop fluid flow along one path in a circuit until enough pressure is generated to push the fluid past the stopping means, or until the stopping means itself is removed or made insignificant. The pressure that is generated because of the stopping means can be utilized to move fluid through the circuit in some creative manner, or to hold fluid at a specific location.
Capillarity is usually represented by the equation h=2"sgr"glcos(xcex8c)grxcfx81 which describes the height (or depth), h, of a fluid within a capillary tube compared to the level of the fluid outside the capillary tube. xcex8c, or the contact angle of the fluid with the capillary tube material, governs whether the fluid in the tube is above or below the level of the fluid outside the tube. If the contact angle of the capillary tube material, with respect to the fluid, is less than 90xc2x0, the material is considered hydrophilic (water liking). If the contact angle of the tube material, with respect to the fluid, is greater than 90xc2x0, the material is considered hydrophobic (water fearing). "sgr"gl represents the surface tension of the fluid with respect to the ambient (usually air) (millijoules/m2), g is the gravitational constant (m/s2), r is the radius of the capillary tube (m), and xcfx81 is the fluid density (kg/m3).
FIGS. 1A-C illustrate the concept of hydrophilicity and hydrophobicity. FIG. 1A illustrates xcex8c. "sgr"gs is the surface tension between a gas and a solid, "sgr"sl is the surface tension between a solid and a liquid, and "sgr"gl is the surface tension between a gas and a liquid. "sgr"gs="sgr"sl+"sgr"glcos(xcex8c). xcex8c (angle in degrees) for water on various materials at around 20xc2x0 C. is shown in Table 1. FIG. 1B illustrates that hydrophilic tubing, such as glass, draws water into the tube. FIG. 1C is similar to FIG. 1B but illustrates that the use of hydrophobic tubing (such as Teflon(copyright)) pushes water away from the tube.
The term xcfx81gh, from the equation for capillarity, is sometimes referred to as the pressure head of a fluid, P (Pa). Re-writing the capillarity equation with respect to P gives P=2"sgr"glcos(xcex8c)/r. In order to effect a stopping means "sgr"gl, xcex8c, r, or a combination of any of the three, needs to change from one side of the stopping means to the other. This will generate a pressure barrier, which causes the fluid to stop until the pressure barrier is overcome or removed. For example, if the radius of a channel were changed in order to effect a stopping means, the equation describing the pressure required to push past the stopping means would be given by xcex94P=2"sgr"glcos(xcex8c)(1/r1xe2x88x921/r2), where r1 is the radius of the channel before the stopping means and r2 is the radius of the channel after the stopping means. This equation is a simplification of the physical system that may be present. A true model would take into consideration the actual channel geometries and other physical/chemical characteristics.
FIG. 1D illustrates a change in channel radius. A channel of radius a changes abruptly to a channel of a smaller radius b. The channel of radius b again changes abruptly to the larger channel of radius a. If the material were hydrophilic the stopping means would be at the point where the channel radius increases in size. In this instance r1 would be given by b and r2 would be given by a. This would generate a positive value for xcex94P, because the cosine of angles between 0 and 90 degrees (the contact angle of the material) is positive. A positive xcex94P suggests a pressure barrier. If the material were hydrophobic the stopping means would be at the point where the channel decreases in size. In this case r1 would be given by a, and r2 by b. A negative cosine value, due to a contact angle greater than 90 degrees, would be multiplied by a negative (1/r1xe2x88x921/r2) term, resulting in a positive xcex94P, or a pressure barrier.
If the contact angle of the material were to change, such as a hydrophilic channel having a hydrophobic region, this can also provide a stopping means. This situation would be characterized by the equation xcex94P=2"sgr"gl[cos(xcex8c1)xe2x88x92cos(xcex8c2)]/r, where xcex8c1 is the contact of the material after the stopping means (hydrophobic). A negative cosine of xcex8c2 would result in a positive xcex94P, signifying a pressure barrier.
A change in surface tension of a fluid flowing through a microfluidic circuit, such as by lining the channel walls with absorbable salts or surfactants, could also generate a stopping means. The equation describing such a pressure barrier would be given by xcex94P=2cos(xcex8c)("sgr"gl1xe2x88x92"sgr"gl2)/r, where "sgr"gl1 is the surface tension of a fluid before the stopping means and "sgr"gl2 is the surface tension of the fluid after the stopping means. In a hydrophobic material the surface tension would need to increase across the stopping means in order to create a pressure barrier.
This invention deals with the passive control of fluids through microfluidic channels using the stopping means described in the previous paragraphs. More specifically, the stopping means derived by reducing the radius, or cross-sectional flow area, of a flow channel containing aqueous based, or polar, fluids in a hydrophobic material, or a material coated with a hydrophobic film. Also encompassed is the control of nonpolar fluids within a hydrophilic material or a material that has been coated with a hydrophilic film. A short channel narrowing, or restriction, with these characteristics can act as a passive valve.
A variety of combinations of channel material and fluid combinations can be used to achieve the desired effect of controlling fluid flow via the use of restrictions or narrowings within microchannels to act as valves. The following are some examples of such useful combinations:
(A) PTFE (Teflon(copyright) or polytetrafluoroethylene), FEP (fluorinated ethylenepropylene), PFA (perfluoralkoxy alkane) or PVDF (polyvinylidene fluoride) as the channel material and polar solutions such as water, saline or buffer solutions not possessing a significant percentage of surfactants, this percentage being known or easily determined by one of skill in the art.
(B) Metals, glass, PMMA (polymethylmethacrylate), polycarbonate, Nylon 6/12 or PVC (polyvinylchloride) as the channel material and non-polar solutions such as hexane, heptane, toluene or benzene.
(C) PTFE, FEP, PFA of PVDF as the channel material with a hydrophilic coating such as Elastophilic(trademark) and non-polar solutions such as those mentioned in (B).
(D) Metals, glass, PMMA, polycarbonate, Nylon 6/12 or PVC as the channel material with a hydrophobic coating such as Teflon(copyright) AF and polar solutions such as those mentioned in (A).
Valving relies upon the fact that the developing flow of a fluid stream requires extra pressure, or work, or energy, to go through a stopping means, and that it would, therefore, preferentially take a path of lesser resistance or stop altogether until enough pressure is built up that forces the fluid through the stopping means. Developing flow is defined as an advancing stream of fluid that possesses a moving interface of solution and air or some other gas. The point of interface is defined as the meniscus. Another characteristic of developing flow is that the surfaces of the flow chamber in front of, or downstream of, the advancing meniscus are not significantly wetted with the fluid that is flowing. Established flow, on the other hand, is where there is no moving meniscus and where all surfaces of the flow channels are significantly wetted.
The scope of this invention is the use of various stopping means that are designed to control the flow of fluid in a network of fluid channels. More specifically this invention details the use of short restrictions, or fluid channel narrowings, designed to control the flow of fluid in a network of hydrophobic fluid channels. The narrowness of the restriction, and its length, depend on the type and extent of fluid control that is required. Generally, however, only a short restriction is desirable so that the restriction itself does not significantly affect established flow in the channel once it becomes established.
The present invention discloses means of controlling the flow of fluids through microchannels in a manner to allow mixing or diluting of the fluids and/or separation of the fluids or a fluid into several channels for multiprocessing. It also discloses various means for consolidating or combining several samples or channels into a fewer number of samples or channels, and the use of air escape channels and stopping means to facilitate complicated fluid processing. The flow of fluid through the microchannels is primarily controlled by restrictions or narrowings purposely placed into the channels, e.g., by micromachining. These restrictions or narrowings act as valves. Unlike valves which require moving parts, the restrictions or narrowings can be static and their function does not depend upon their motion. Flow of fluid through the microchannels can also be controlled by changing the contact angle or the surface tension, e.g., by including films of salts or surfactants or by a hydrophobic patch in an otherwise hydrophilic channel.